Mycobacterium leprae is an obligate human parasite which has yet to be cultured successfully in vitro. The lack of convenient cultural and laboratory infection models of this disease has greatly limited leprosy research. As a result, most of the immunological studies have had to be carried out using human patients, with all of the difficulties and experimental limitations that it entails. Alternative infectious mouse models using M. lepraemurium or M. marinum have some experimental advantage over M. leprae but have not proven to be a completely satisfactory answer to the problem. Several members of the M. avium-intracellulare complex are capable of giving rise to heavy persisting systemic infections in mice which seem to be unable to develop an effective anti-Mycobacterial type of immune response. Many of these bacilli exhibit little virulence for normal mice despite the presence of massive bacterial populations within the RES. Histological examination of the lesions in the lung, liver, spleen and several lymph nodes disclose at least a superficial similarity to that seen in human leprosy. The observed similarities were sufficient to justify a detailed examination of this infection as a possible model of lepromatous leprosy. Purified protein derivatives (PPD), purified cytoplasmic proteins and lepromin-type whole cell antigens will be prepared and used to study the anergic response which develops in both actively infected and adoptively sensitized mice. Finally, the effect of immunotherapy on the Mycobacterial infection will be assessed in terms of restored delayed hypersensitivity, recovery from Mitsuda anergy and the expression of an effective anti-Mycobacterial immunity capable of eventually eliminating the organisms from the host tissues.